Maternal and Early Postnatal Immune Activation Produce Dissociable Effects on Neurotransmission in mPFC-Amygdala Circuits

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Yan LiVadim Y Bolshakov

Abstract

Inflammatory processes may be involved in the pathophysiology of neuropsychiatric illnesses including autism spectrum disorder (ASD). Evidence from studies in rodents indicates that immune activation during early development can produce core features of ASD (social interaction deficits, dysregulation of communication, increases in stereotyped behaviors, and anxiety), although the neural mechanisms of these effects are not thoroughly understood. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, or vehicle on gestational day 12.5 to produce maternal immune activation (MIA). Male offspring received either vehicle or lipopolysaccharide, which simulates a bacterial infection, on postnatal day 9 to produce postnatal immune activation (PIA). We then used optogenetics to address the possibility that early developmental immune activation causes persistent alterations in the flow of signals within the mPFC to basolateral amygdala (BLA) pathway, a circuit implicated in ASD. We found that our MIA regimen produced increases in synaptic strength in glutamatergic projections from the mPFC to the BLA. In contrast, our PIA regimen produced decreases in feedforward GABAergic inhibi...Continue Reading

Citations

Nov 6, 2018·Cerebral Cortex·Amandine FernandezYehezkel Ben-Ari
Jan 6, 2019·Molecular Psychiatry·Galen MissigWilliam A Carlezon
Aug 28, 2020·Frontiers in Neuroscience·Marissa R KeeverSandra L Rodriguez-Zas
Jul 28, 2019·International Journal of Molecular Sciences·Theoharis C TheoharidesIrene Tsilioni
Sep 21, 2018·Frontiers in Immunology·Yeonwoo LebovitzMichelle H Theus
May 7, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Galen MissigWilliam A Carlezon
May 22, 2021·Behavioural Brain Research·Arthur Rocha-GomesHércules Ribeiro Leite
Dec 18, 2021·Frontiers in Cellular Neuroscience·Haley A VecchiarelliMatthew N Hill

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